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Expression of brx proto-oncogene in normal ovary and in epithelial ovarian neoplasms
B T Miller1, D M Rubino, P H Driggers
1Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Objective:
We previously identified a protein, Brx, that interacted with estrogen receptor alpha. Sequence analysis determined that Brx is a novel member of the Dbl family of oncoproteins involved in signaling pathways that regulate cell growth. Because the Brx protein was found to be highly expressed in hormoneresponsive breast epithelium, the objective of this study was to determine whether Brx was expressed in both normal and neoplastic ovarian tissues.
Study Design:
A polyclonal antiserum directed against the Brx protein was used to perform immunolocalization on sections from 5 normal ovaries and 20 ovarian neoplasms. Chromosomal localization of the brx gene was accomplished by means of fluorescence in situ hybridization. Northern and Western blot analyses were performed on extracts prepared from human ovaries.
Results:
Brx protein was localized to the cytoplasm of granulosa cells from mature graafian follicles, the corpus luteum, and islands of hilar cells in normal ovaries. In tumors with low malignant potential and ovarian carcinomas the neoplastic epithelium stained strongly for Brx protein. Northern and Western blot analyses, respectively, confirmed expression of Brx messenger ribonucleic acid and protein in normal ovary. Finally, the brx gene was localized to 15q25.
Conclusion:
The proto-oncogene brx is expressed in specific normal human ovarian tissues and is also present in ovarian epithelial neoplasms.
Insights
The proto-oncogene Brx is expressed in normal ovarian tissues and ovarian neoplasms. This finding suggests Brx may play a role in ovarian cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Brx, a novel Dbl family oncoprotein, interacts with estrogen receptor alpha.
- Brx is involved in cell growth signaling pathways.
- High Brx expression in breast epithelium suggests a role in hormone-responsive cancers.
Purpose of the Study:
- To determine Brx expression in normal and neoplastic ovarian tissues.
- To investigate the role of Brx in ovarian cancer.
Main Methods:
- Immunolocalization using anti-Brx antiserum on ovarian tissue sections.
- Fluorescence in situ hybridization for chromosomal localization of the brx gene.
- Northern and Western blot analyses for gene and protein expression.
Main Results:
- Brx protein detected in granulosa cells, corpus luteum, and hilar cells of normal ovaries.
- Strong Brx staining in neoplastic epithelium of low malignant potential tumors and carcinomas.
- Brx mRNA and protein confirmed in normal ovarian extracts.
- The brx gene localized to chromosome 15q25.
Conclusions:
- The proto-oncogene brx is expressed in specific normal ovarian tissues.
- Brx is also present in ovarian epithelial neoplasms.
- Brx expression in ovarian neoplasms warrants further investigation into its role in ovarian cancer.